{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:49:06Z","timestamp":1792500546507,"version":"4.5.0"},"reference-count":60,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018694","name":"European Commission","doi-asserted-by":"publisher","award":["101072531"],"award-info":[{"award-number":["101072531"]}],"id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Toxicokinetic-toxicodynamic (TKTD) models are increasingly used to enhance environmental risk assessment by linking laboratory toxicity data with dynamic exposure scenarios. For freshwater microalgae, which are crucial primary producers, TKTD approaches offer a framework to predict population growth inhibition and recovery under fluctuating chemical stress. A review of 12 studies (2012\u20132023) applying TKTD models to freshwater planktonic microalgae was conducted to compare their structural assumptions, end points, and validation methods. These models mainly focus on green algae and herbicides that inhibit photosystem II, with limited exploration of other taxonomic groups or modes of action. The complexity of models varies significantly, from simple structures assuming rapid equilibrium between external and internal chemical concentrations to mechanistic models that explicitly incorporate TK components and damage progression. While simple models support regulatory use, omitting TK processes can reduce their effectiveness for chemicals with delayed effects or complex uptake behaviors. Expanding taxonomic coverage and enhancing external validation under realistic exposure conditions is crucial to increasing the ecological relevance of algal TKTD modeling.<\/jats:p>","DOI":"10.1021\/acs.est.6c05753","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:01:38Z","timestamp":1791421298000},"page":"29229-29244","source":"Crossref","is-referenced-by-count":0,"title":["Current\nStrengths\nand Limitations of Toxicokinetic-Toxicodynamic\n(TKTD) Models for Freshwater Microalgae"],"prefix":"10.1021","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1616-966X","authenticated-orcid":true,"given":"Emma","family":"Yenney","sequence":"first","affiliation":[{"name":"University of Copenhagen , , Thorvaldsensvej 40 , ,","place":["Frederiksberg C, Denmark, 1871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4724-9447","authenticated-orcid":true,"given":"Nina","family":"Cedergreen","sequence":"additional","affiliation":[{"name":"University of Copenhagen , , Thorvaldsensvej 40 , ,","place":["Frederiksberg C, Denmark, 1871"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"2026102007521153700_cit1","unstructured":"European Parliament, Council of the European Union.\n          \n          Regulation\n(EC) No 1107\/2009 of the European\nParliament and of the Council of 21 October 2009 Concerning the Placing\nof Plant Protection Products on the Market and Repealing Council Directives\n79\/117\/EEC and 91\/414\/EEC, 2009."},{"issue":"7","key":"2026102007521153700_cit2","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2013.3290","article-title":"Guidance on tiered risk assessment\nfor plant protection products for aquatic organisms in edge-of-field\nsurface waters","volume":"11","author":"EFSA Panel on Plant Protection Products and their Residues (PPR).","year":"2013","journal-title":"EFSA J."},{"key":"2026102007521153700_cit3","doi-asserted-by":"publisher","first-page":"18042","DOI":"10.1021\/acs.est.5c04027","article-title":"Comparative Evaluation of Toxicity\nEnd Points in Unicellular Bioassays for Environmental Pollutant Assessment","volume":"59","author":"Wang","year":"2025","journal-title":"Environ. Sci. Technol."},{"key":"2026102007521153700_cit4","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2018.0252","article-title":"Sensitivity of freshwater species\nunder single and multigenerational exposure to seawater intrusion","volume":"374","author":"Vena\u0302ncio","year":"2019","journal-title":"Philos. Trans. R. 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Toxicol."},{"key":"2026102007521153700_cit8","doi-asserted-by":"publisher","DOI":"10.3390\/toxics12120905","article-title":"Integration of Copper\nToxicity Mechanisms in Raphidocelis\nsubcapitata: Advancing Insights at Environmentally Relevant Concentrations","volume":"12","author":"Machado","year":"2024","journal-title":"Toxics"},{"key":"2026102007521153700_cit9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ecolmodel.2013.01.017","article-title":"Mechanistic TK\/TD-model\nsimulating the effect of growth inhibitors on Lemna populations","volume":"255","author":"Schmitt","year":"2013","journal-title":"Ecol. Modell."},{"key":"2026102007521153700_cit10","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1021\/es103092a","article-title":"General Unified Threshold\nModel of Survival - a Toxicokinetic-Toxicodynamic Framework for Ecotoxicology","volume":"45","author":"Jager","year":"2011","journal-title":"Environ. Sci. 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Plant Manage."},{"key":"2026102007521153700_cit50","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.envpol.2018.03.003","article-title":"Aquatic plants: Test species sensitivity and minimum\ndata requirement evaluations for chemical risk assessments and aquatic\nlife criteria development for the USA","volume":"238","author":"Lewis","year":"2018","journal-title":"Environ.\nPollut."},{"key":"2026102007521153700_cit51","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecolind.2023.109875","article-title":"Identification of major environmental\nfactors driving phytoplankton community succession before and after\nthe regime shift of Erhai Lake, China","volume":"146","author":"Yang","year":"2023","journal-title":"Ecol.\nIndic."},{"key":"2026102007521153700_cit52","doi-asserted-by":"publisher","first-page":"4359","DOI":"10.1007\/s10750-019-04087-y","article-title":"Mitigating eutrophication and toxic cyanobacterial blooms in large\nlakes: The evolution of a dual nutrient (N and P) reduction paradigm","volume":"847","author":"Paerl","year":"2020","journal-title":"Hydrobiologia"},{"key":"2026102007521153700_cit53","doi-asserted-by":"publisher","first-page":"339","DOI":"10.2307\/1961640","article-title":"The Dynamics\nof Fresh-water Plankton Populations","volume":"16","author":"Pennak","year":"1946","journal-title":"Ecol. 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Plant Sci."},{"key":"2026102007521153700_cit56","unstructured":"Toxicity and Assessment of Chemical Mixtures, Directorate\nGeneral for Health and Consumers, European Commission2012."},{"key":"2026102007521153700_cit57","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1021\/acs.est.0c05282","article-title":"Predicting Mixture\nEffects over Time with Toxicokinetic\u2013Toxicodynamic\nModels (GUTS): Assumptions, Experimental Testing, and Predictive Power","volume":"55","author":"Bart","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"2026102007521153700_cit58","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1002\/etc.5034","article-title":"Correlated Ni, Cu, and Zn Sensitivities of 8 Freshwater\nAlgal Species and Consequences for Low-Level Metal Mixture Effects","volume":"40","author":"Fettweis","year":"2021","journal-title":"Environ. Toxicol. Chem."},{"key":"2026102007521153700_cit59","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.157048","article-title":"How to analyse\nand account for interactions in mixture toxicity with toxicokinetic-toxicodynamic\nmodels","volume":"843","author":"Bart","year":"2022","journal-title":"Sci. Total Environ."},{"key":"2026102007521153700_cit60","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2020.106206","article-title":"Ten years\nof research on synergisms and antagonisms in chemical mixtures: A\nsystematic review and quantitative reappraisal of mixture studies","volume":"146","author":"Martin","year":"2021","journal-title":"Environ. Int."}],"container-title":["Environmental\nScience &amp;\nTechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.est.6c05753","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/60\/41\/29229\/68779693\/acs.est.6c05753.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/60\/41\/29229\/68779693\/acs.est.6c05753.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:20:18Z","timestamp":1792498818000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/esthag\/article\/60\/41\/29229\/5446630\/Current-Strengths-and-Limitations-of-Toxicokinetic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":60,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2026,10,7]]},"published-print":{"date-parts":[[2026,10,20]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.est.6c05753","relation":{},"ISSN":["0013-936X","1520-5851"],"issn-type":[{"value":"0013-936X","type":"print"},{"value":"1520-5851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]}}}